NCF1

Variants (also known as mutations) in the NCF1 gene account for about 25 percent of cases of chronic granulomatous disease. People with this disorder are at increased risk of developing recurrent episodes of infection and inflammation due to a weakened immune system. The variants that cause this disorder occur in both copies of the NCF1 gene in each cell. Ninety-five percent of affected individuals have a variant known as delta GT that deletes two DNA building blocks from the NCF1 gene in an area called exon 2 (written as 75_76delGT). This genetic change leads to the production of an abnormally short, nonfunctional version of neutrophil cytosolic factor 1. Other, less common variants also disrupt the function or production of neutrophil cytosolic factor 1. Without this protein, NOX cannot assemble or function properly. As a result, phagocytes are unable to produce ROS to kill foreign invaders, and neutrophil activity is not regulated. A lack of NOX leaves affected individuals vulnerable to many types of infection and excessive inflammation.

The NCF1 gene is located in a region of chromosome 7 that is often deleted in people with Williams syndrome. Williams syndrome is a developmental disorder that affects many parts of the body. As a result of the deletion of part of chromosome 7, some people with this condition are missing one copy of the NCF1 gene in each cell. Researchers have found that the loss of this gene is a protective factor that appears to lower the risk of developing high blood pressure (hypertension). People with Williams syndrome whose NCF1 gene is not deleted have a higher risk of developing hypertension.

People with only one copy of the NCF1 gene have reduced levels of the neutrophil cytosolic factor 1 protein, which decreases the activity of NOX and results in the production of fewer ROS. Studies suggest that ROS play an important role in blood vessel changes related to hypertension.